Poly(ethylene glycol)-poly(L-lactide) diblock copolymer prevents aggregation of poly(L-lactide) microspheres during ethylene oxide gas sterilization

Sterilization procedure is one of the must important obstacles in the clini cal applications of biodegradable microspheres. The microspheres prepared w ith poly(alpha -hydroxy acid) were severely aggregated during ethylene oxid e (EO) gas sterilization, and could not be used in clinical applications. I n this study, the effects of EO gas sterilization on the poly(L-lactide) (P LLA) microspheres were analyzed by nuclear magnetic resonance spectroscopy (H-1 down arrow NMR), diff'erential scanning calorimetry (DSC), gel permeat ion chromatography (GPC), scanning electron microscope (SEM) and size fract ionation. The aggregation between the microspheres might be stimulated by h igh mobility of amorphous regions of PLLA on the microsphere surfaces since both water vapor and gas mixture can reduce glass transition temperature ( T-g) of PLLA below the sterilization temperature. During EO gas sterilizati on, there were no changes in the molecular structure and the molecular weig ht of PLLA in microspheres, but there were changes in the crystallinity of PLLA in microspheres. In this study, poly(L-lactide)-poly(ethylene glycol) diblock copolymers (PLE) were blended with PLLA homopolymers in various rat ios to design the microsphere suitable for EO gas sterilization. Aggregatio n of PLLA microspheres was markedly prevented when more than 4wt% of PLE wa s blended in the microspheres. This inhibition effect on aggregation may be due to the increased initial crystallinity of the microspheres, which help to maintain the microsphere morphology during EO gas sterilization. (C) 20 01 Published by Elsevier Science Ltd.